CTBP1

Chr 4AD

C-terminal binding protein 1

Also known as: BARS, HADDTS

NCBI Gene: 1487ENSG00000159692UniProt: Q13363

This gene encodes a protein that binds to the C-terminus of adenovirus E1A proteins. This phosphoprotein is a transcriptional repressor and may play a role during cellular proliferation. This protein and the product of a second closely related gene, CTBP2, can dimerize. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Hypotonia, ataxia, developmental delay, and tooth enamel defect syndromeMIM #617915
AD
1
Active trials
121
Pathogenic / LP
484
ClinVar variants
33
Pubs (1 yr)
3.3
Missense Z· constrained
0.28
LOEUF· LoF intolerant
Clinical Summary— CTBP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
121 Pathogenic / Likely Pathogenic· 154 VUS of 484 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.28LOEUF
pLI 0.984
Z-score 3.60
OE 0.06 (0.02–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.31Z-score
OE missense 0.45 (0.39–0.52)
126 obs / 282.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.02–0.28)
0≤0.351.4
Missense OE0.45 (0.39–0.52)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 1 / 17.0Missense obs/exp: 126 / 282.5Syn Z: 0.02
LOFDN
DN
0.4389th %ile
GOF
0.5465th %ile
LOF
0.71top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.28
DN1 literature citation

Literature Evidence

DNDecreased complex I and IV activities in skeletal muscle of our patient suggests that BAX expression is altered by mutated CtBP1, with the c.991C>T p.(Arg331Trp) variant acting in a dominant-negative mechanism to disrupt mitochondrial function.PMID:28955726

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

484 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic114
Likely Pathogenic7
VUS154
Likely Benign187
Benign14
Conflicting8
114
Pathogenic
7
Likely Pathogenic
154
VUS
187
Likely Benign
14
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
113
0
114
Likely Pathogenic
0
0
7
0
7
VUS
5
117
29
3
154
Likely Benign
0
10
71
106
187
Benign
0
0
10
4
14
Conflicting
—8
Total5128230113484

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

CTBP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CTBP1-related hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome

strong
ADLoss Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
stop gainedmissense variantframeshift variant NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients